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From SNPedia

Geno Mag Summary
(C;C) 0 normal
(C;T) complex; see details
(T;T) 2.5 complex; see details
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs4986791
23andMe allrs4986791
SNP Nexus

GWAS Ctlgrs4986791
Max Magnitude2.5
? (C;C) (C;T) (T;T) 28
rs4986791, a SNP also known as Thr399Ile (and also 1196C/T) in the TLR4 gene, is often studied along with a cosegregating SNP known as Asp299Gly, rs4986790. (TLR4 encodes a receptor involved in the innate immune response.) Together, these SNPs have been reported to be associated with a wide variety of both infectious and non-infectious diseases, although there are conflicting or even contradictory results also reported in some cases. The risk allele for rs4986791 is (T).

Reported associations include [PMID 15766650]:

  • Heart disease
    • Men with the risk alleles for both SNPs are at increased risk for myocardial infarction in this study of over 2000 individuals. [PMID 15576653]
    • rs4986790(G) carriers are not at increased risk for myocardial infartions, at least in this study of ~200 individuals. [PMID 15547160]
    • rs4986790(G) carriers are less likely to have heart attacks, in this study of ~400 individuals. [PMID 14563652]
    • Individuals with the risk alleles for both SNPs have a lower incidence of carotid stenosis [PMID 12124407]
  • Allograft complications
    • A study of 300+ recipients of hematopoietic-cell transplants concluded that the adjusted hazard ratio for a recipient of developing a life-threatening invasive aspergillosis infection was 6.16x higher (CI: 1.97-19.26, p=0.002) if the donor carried these TLR4 risk alleles. This risk was statistically significant for unrelated recipients of transplants (odds ratio, 5.0, CI: 1.04-24.01, p=0.04) but did not quite meet the p=0.05 significance criteria for related recipients (odds ratio, 2.29, CI: 0.93-5.68, p=0.07). [PMID 18946062OA-icon.png]
[PMID 21283657OA-icon.png] Gallbladder Cancer Predisposition: A Multigenic Approach to DNA-Repair, Apoptotic and Inflammatory Pathway Genes

[PMID 21081146] Impact of Toll-like receptor 4 polymorphisms on risk of cancer

[PMID 21837802] Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African Children

[PMID 22286521] Polymorphism of the TLR4 Gene Reduces the Risk of Hepatitis C Virus-Induced Hepatocellular Carcinoma

[PMID 22645142OA-icon.png] Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy

Risk rs4986791(T;T)
Alt rs4986791(T;T)
Reference rs4986791(C;C)
Significance Non-pathogenic
Disease TLR4 POLYMORPHISM not provided
Variation info
Gene TLR4
Reversed 0
HGVS NC_000009.11:g.120475602C>T
CLNSRC OMIM Allelic Variant
CLNACC RCV000007043.3, RCV000086999.1,

[PMID 16820586OA-icon.png] Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

[PMID 16954131] Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population.

[PMID 17667860] Toll-like receptor 2 polymorphism is associated with preterm birth.

[PMID 17699831OA-icon.png] Toll-like receptor 4 polymorphism associated with the response to whole-cell pertussis vaccination in children from the KOALA study.

[PMID 18172114OA-icon.png] Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration.

[PMID 18298826OA-icon.png] Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol.

[PMID 18307517OA-icon.png] Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans.

[PMID 18325643OA-icon.png] Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results.

[PMID 18382655OA-icon.png] Maternal TLR4 and NOD2 gene variants, pro-inflammatory phenotype and susceptibility to early-onset preeclampsia and HELLP syndrome.

[PMID 18396467OA-icon.png] Genetic variation and haplotype structures of innate immunity genes in eastern India.

[PMID 18422738OA-icon.png] Study of Toll-like receptor gene loci in sarcoidosis.

[PMID 18549840OA-icon.png] Cholesterol ester transfer protein, interleukin-8, peroxisome proliferator activator receptor alpha, and Toll-like receptor 4 genetic variations and risk of incident nonfatal myocardial infarction and ischemic stroke.

[PMID 18753640OA-icon.png] Toll-like receptor 3 and geographic atrophy in age-related macular degeneration.

[PMID 18975326] Toll-like receptor 2 variants are associated with acute reactive arthritis.

[PMID 18987746OA-icon.png] Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination.

[PMID 19085953OA-icon.png] Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses.

[PMID 19134200OA-icon.png] No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis.

[PMID 19277200OA-icon.png] Toll-like receptor 4 (TLR4) and typhoid fever in Vietnam.

[PMID 19543401OA-icon.png] Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women.

[PMID 19567509OA-icon.png] Genetic variants and prostate cancer risk: candidate replication and exploration of viral restriction genes.

[PMID 19586676OA-icon.png] Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection.

[PMID 20011079OA-icon.png] Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan.

[PMID 20016852OA-icon.png] Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women.

[PMID 20026892] [Association of Toll-like receptor gene with Crohn's disease in Koreans].

[PMID 20463618OA-icon.png] Role of polymorphic variants as genetic modulators of infection in neonatal sepsis.

[PMID 20492496] Significant association between toll-like receptor gene polymorphisms and gallbladder cancer.

[PMID 20525286OA-icon.png] Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts.

[PMID 20671584] Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention.

[PMID 21385363OA-icon.png] Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.

[PMID 22300618] Toll-like 4 receptor variant, Asp299Gly, and reduced risk of hemorrhagic cystitis after hematopoietic stem cell transplantation.

[PMID 22348075OA-icon.png] Influence of common non-synonymous Toll-like receptor 4 polymorphisms on bronchopulmonary dysplasia and prematurity in human infants.

GET Evidence
aa_change Thr399Ile
aa_change_short T399I
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.0474066

[PMID 23084080] The TLR4 gene polymorphisms and susceptibility to cancer: A systematic review and meta-analysis

[PMID 22494793] Innate immunity gene single nucleotide polymorphisms and otitis media

[PMID 23151015OA-icon.png] Toll-like receptor 3 gene polymorphisms and severity of pandemic A/H1N1/2009 influenza in otherwise healthy children

[PMID 23086128] Profiles of gene polymorphisms in cytokines and Toll-like receptors with higher risk for gastric cancer

[PMID 23867959OA-icon.png] Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants

[PMID 24028589] TLR2, TLR3, TLR4 and CD14 gene polymorphisms associated with oral lichen planus risk

[PMID 24447403] TLR4 polymorphism is not associated with biopsy proven giant cell arteritis

[PMID 23071570OA-icon.png] Gene-gene interaction and functional impact of polymorphisms on innate immune genes in controlling Plasmodium falciparum blood infection level.

[PMID 23161283OA-icon.png] SNPs in toll-like receptor (TLR) genes as new genetic alterations associated with congenital toxoplasmosis?

[PMID 23289617] Genetic variation of TLR2 and TLR4 among the Saudi Arabian population: insight into the evolutionary dynamics of the Arabian Peninsula.

[PMID 23417289] Coding variants of TLR2 and TLR4 genes do not substantially contribute to prosthetic joint infection.

[PMID 23459936OA-icon.png] Exploring the genetic basis of chronic periodontitis: a genome-wide association study.

[PMID 25177689OA-icon.png] The Association of Toll-Like Receptor 4 Polymorphism with Hepatitis C Virus Infection in Saudi Arabian Patients

[PMID 25213166] An association between single nucleotide polymorphisms within TLR and TREM-1 genes and infective endocarditis

[PMID 24349054OA-icon.png] No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV

[PMID 25360682OA-icon.png] Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis

[PMID 26919710] Variations in genes involved in regulation of the nuclear factor - κB pathway and the risk of acute myeloid leukaemia.

[PMID 25542762] Poststroke fatigue: hints to a biological mechanism.

[PMID 27069792] Association of NOD1, CXCL16, STAT6 and TLR4 gene polymorphisms with Malaysian patients with Crohn's disease

[PMID 27155792] TLR2 and TLR4 polymorphisms in Southern Chinese Psoriasis Vulgaris patients.

[PMID 27526043] Lack of Association Between Polymorphism rs4986791 in TLR4 and Primary Open-Angle Glaucoma in a Saudi Cohort.